Ductal adenocarcinoma of the pancreas with intratumoral calcification

We present two cases of ductal adenocarcinoma of the pancreas with intratumoral calcification. The two cases indicate two different etiologies for intratumoral calcification in ductal adenocarcinoma. Thus, the possibility of adenocarcinoma should be considered when a tumor with intratumoral calcification is found, although the incidence of intratumoral calcification in the ductal adenocarcinoma of the pancreas remains rare.     

高分子量细胞角蛋白及前列腺特异性抗原在前列腺腺癌中的表达和意义

目的:提高对各种前列腺良恶性病变的认识和鉴别诊断水平。方法:采用免疫组织化学染色对213例前列腺良恶性病变组织分别作高分子量细胞角蛋白34BE12和前列腺特异性抗原(PSA)标记,特异地显示前列腺基底细胞并间接了解基细胞层的完整性。结果:前列腺腺癌基底细胞均丢失,而前列腺增生性病变基底细胞绝大多数保存完好,只有少数3级前列腺上皮内肿瘤和非典型性瘤样增生基底细胞不完整。对PSA染色,大多数前列腺腺癌表达低,少数分化好的癌组织呈阳性,而良性前列腺增生组织标本中PSA表达高。结论:研究表明,联合应用高分子量细胞角蛋白34BE12及PSA标记物,在前列腺良恶性病变的鉴别诊断及肿瘤恶性程度的判断中均有很好的应用价值。     

Role of ProstaScint for brachytherapy in localized prostate adenocarcinoma

ProstaScint (CYT-356 or capromab pendetide, Cytogen) is an 111In-labeled monoclonal mouse antibody specific for prostate-specific membrane antigen, a prostate transmembrane glycoprotein that is upregulated in prostate adenocarcinoma. ProstaScint scans are US Food and Drug Administration approved for pretreatment evaluation of metastatic disease in high-risk patients. They are also approved for post-prostatectomy assessment of recurrent disease in patients with a rising prostate-specific antigen level. This review explores the literature on ProstaScint and its use in guiding the treatment of prostate cancer. A novel technique for identifying areas of cancer within the prostate using ProstaScint images fused with pelvic computed tomography scans is also described. The identification of areas of high antibody signal provides targets for radiotherapeutic dose escalation, with the overall goals of improving treatment outcome while preserving adjacent tissue structures and decreasing treatment morbidity.     

Protease nexin 1 inhibits hedgehog signaling in prostate adenocarcinoma

Prostate adenocarcinoma (CaP) patients are classified into low-, intermediate-, and high-risk groups that reflect relative survival categories. While there are accepted treatment regimens for low- and high-risk patients, intermediate-risk patients pose a clinical dilemma, as treatment outcomes are highly variable for these individuals. A better understanding of the factors that regulate the progression of CaP is required to delineate risk. For example, aberrant activation of the Hedgehog (Hh) pathway is implicated in CaP progression. Here, we identify the serine protease inhibitor protease nexin 1 (PN1) as a negative regulator of Hh signaling in prostate. Using human CaP cell lines and a mouse xenograft model of CaP, we demonstrate that PN1 regulates Hh signaling by decreasing protein levels of the Hh ligand Sonic (SHH) and its downstream effectors. Furthermore, we show that SHH expression enhanced tumor growth while overexpression of PN1 inhibited tumor growth and angiogenesis in mice. Finally, using comparative genome hybridization, we found that genetic alterations in Hh pathway genes correlated with worse clinical outcomes in intermediate-risk CaP patients, indicating the importance of this pathway in CaP.     

MRI features of mucinous adenocarcinoma of the prostate: report of four cases

Abdominal Radiology - We report four patients with mucinous adenocarcinoma of the prostate, focusing on their magnetic resonance imaging (MRI) findings. The lesions appeared hyperintense on...     

Immunohistochemical differential diagnosis between urothelial carcinoma and prostate adenocarcinoma among Egyptian patients

The aim of the present study was to differentiate between prostate adenocarcinoma and urothelial carcinoma among Egyptian patients by immunohistochemical methods. Two groups of patients were used: urothelial group, consisted of 9 cystitis, 21 transitional cell carcinoma (TCC) and 5 urinary bladder mucoid adenocarcinoma (MAC) and prostatic group, consisted of 9 nodular prostatic hyperplasia (NPH) and 21 prostatic adenocarcinoma (PAC). H–E stained sections were performed to confirm the diagnosis and evaluate the histopathological characteristics of the tumor. Immunohistochemical techniques were used for detection of P63, CK7, CK10 and PSA. The results showed that in urothelial group, positive p63and CK7 immunostaining was observed in all cases of cystitis, transitional cell carcinoma and urinary bladder mucoid adenocarcinoma. All cases of cystitis, transitional cell carcinoma and urinary bladder mucoid adenocarcinoma were CK10 and PSA negative. In prostate group, positive p63 immunostaining was observed in all cases of NPH and in prostatic adenocarcinoma. Positive CK7 immunostaining was observed in all cases of NPH while all cases of prostatic adenocarcinoma were CK7 negative. Positive CK10 immunostaining was observed in all cases of NPH. In prostatic adenocarcinoma, 11 cases were CK10 positive and 10 cases were CK10 negative. All cases of NPH and prostatic adenocarcinoma were PSA positive. In conclusion, the result of the present work proved that p63 and CK7 can be used along with other markers to differentiate between adenocarcinoma of prostate and urothelial carcinoma of the bladder. Also, CK10 and PSA are useful for distinguishing prostate cancer from urothelial carcinoma.     

In situ gene therapy for adenocarcinoma of the prostate: a phase I clinical trial.

For patients with local recurrence of prostate cancer after definitive irradiation therapy there is no treatment widely considered safe and effective. After extensive preclinical testing of prodrug gene therapy in vitro and in vivo, we conducted a phase I dose escalation clinical trial of intraprostatic injection of a replication-deficient adenovirus (ADV) containing the herpes simplex virus thymidine kinase gene (HSV-tk) injected directly into the prostate, followed by intravenous administration of the prodrug ganciclovir (GCV). Our goal was to determine safe dose levels of the vector for future trials of efficacy. Patients with a rising serum prostate-specific antigen (PSA) level and biopsy confirmation of local recurrence of prostate cancer without evidence of metastases one or more years after definitive irradiation therapy were eligible for the trial. After giving informed consent, patients received injections of increasing concentrations of ADV/HSA-tk in 1 ml into the prostate under ultrasound guidance. Ganciclovir was then given intravenously for 14 days (5 mg/kg every 12 hr). Patients were monitored closely for evidence of toxicity and for response to therapy. Eighteen patients were treated at 4 escalating doses: group 1 (n = 4) received 1 x 10(8) infectious units (IU); group 2 (n = 5) received 1 x 10(9) IU; group 3 (n = 4) received 1 x 10(10) IU; group 4 (n = 5) received 1 x 10(11) IU. Vector was detected by PCR of urine samples after treatment, increasing in frequency and duration (up to 32 days) as the dose increased. All cultures of blood and urine specimens were negative for growth of adenovirus. Minimal toxicity (grade 1-2) was encountered in four patients. One patient at the highest dose level developed spontaneously reversible grade 4 thrombocytopenia and grade 3 hepatotoxicity. Three patients achieved an objective response, one each at the three highest dose levels, documented by a fall in serum PSA levels by 50% or more, sustained for 6 weeks to 1 year. This study is the first to demonstrate the safety of ADV/HSV-tk plus GCV gene therapy in human prostate cancer and the first to demonstrate anticancer activity of gene therapy in patients with prostate cancer. Further trials are underway to identify the optimal distribution of vector within the prostate and to explore the safety of repeat courses of gene therapy.     

Frequency-domain analysis of photoacoustic imaging data from prostate adenocarcinoma tumors in a murine model

Photoacoustic imaging is an emerging technique for anatomical and functional sub-surface imaging but previous studies have predominantly focused on time-domain analysis. In this study, frequency-domain analysis of the radio-frequency signals from photoacoustic imaging was performed to generate quantitative parameters for tissue characterization. To account for the response of the imaging system, the photoacoustic spectra were calibrated by dividing the photoacoustic spectra (radio-frequency ultrasound spectra resulting from laser excitation) from tissue by the photoacoustic spectrum of a point absorber excited under the same conditions. The resulting quasi-linear photoacoustic spectra were fit by linear regression and midband fit, slope and intercept were computed from the best-fit line. These photoacoustic spectral parameters were compared between the region-of-interests (ROIs) representing prostate adenocarcinoma tumors and adjacent normal flank tissue in a murine model. The mean midband fit and intercept in the ROIs showed significant differences between cancerous and noncancerous regions. These initial results suggest that such frequency-domain analysis can provide a quantitative method for tumor tissue characterization using photoacoustic imaging in vivo. (E-mail: cxdeng@umich.edu and xdwang@umich.edu)     

Real-time RT-PCR for the measurement of prostate-specific antigen mRNA expression in benign hyperplasia and adenocarcinoma of prostate.

Since PSA is supposed to play an active role in the progression of prostate cancer, we applied a quantitative RT-PCR to measure the absolute levels of prostate-specific antigen (PSA) mRNA expression in benign and malignant prostatic tissue. Consecutive fine needle prostate biopsy material from 59 patients (43 with prostate adenocarcinoma and 16 with benign prostatic hyperptrophy; BPH) was used for the measurement of PSA mRNA expression. In addition, we evaluated the correlation between PSA synthesis and PSA circulating levels in the same patients. The relationship between PSA mRNA expression and histological grade was also evaluated. PSA mRNA was measured with a quantitative RT-PCR, based on the use of fluorogenic probes, according to the TaqMan reaction system. The mRNA expression for PSA in prostate adenocarcinoma biopsies was highly variable, ranging from 2 x 10(4) to 2.1 x 10(8) molecules/microg total RNA with a mean value of 2.5 x 10(7) and significantly higher (p = 0.006) than that found in BPH patients (mean: 1.3 x 10(6) and range: 6.9 x 10(2) to 8 x 10(6)). The mRNA PSA expression in needle biopsy material did not seem to be related to PSA circulating levels in prostate cancer patients (r = 0.281), whereas in BPH patients the two parameters correlated significantly (r = 0.667, p < 0.01). A reduction of PSA mRNA expression in samples with a lower grade of differentiation (Gleason score 9-10) was also observed. Even though a mean increase of PSA expression was demonstrated in cancer samples, this small difference does not confirm a significant role of PSA proteolytic activity in prostate cancer progression. In conclusion, the assay procedure we proposed represents a reliable basis for more extensive study of PSA physiopathology in prostate cancer.     

转基因小鼠前列腺癌及转移的三维超声微成像

目的:应用三维超声微成像检测转基因小鼠前列腺腺癌(TGMAP)模型的前列腺肿瘤和转移。方法:使用三维超声微成像系统监测TGMAP模型小鼠的前列腺肿瘤生长。通过对TGMAP小鼠前列腺癌的三维超声图像和前列腺癌标本的比较,验证该超声系统检测活体小鼠肿瘤大小的可靠性。结果:超声成像可检测到直径为2.4～14mm的肿瘤和转移。通过三维超声体内测量与尸检获得的肿瘤最大直径的相关系数为0.998,超声诊断的敏感性和特异性均>90%。结论:TGMAP模型的三维超声微成像有望成为小鼠临床前期研究的新的微成像手段。     

Extremely high values of prostate-specific antigen in patients with adenocarcinoma of the prostate; demonstration of the "hook effect"

We reviewed 721 consecutive samples submitted for measurement of prostate-specific antigen (PSA) over five months. We identified three patients with extremely high PSA concentrations: 650, 1840, and 3280 micrograms/L (their acid phosphatase activities were 3.2, 1337, and 2.8 U/L, respectively), and present case reports for the latter two. Serial dilutions of samples obtained from the patient with the highest PSA concentration indicated that the one-step Tandem-PSA assay gave falsely low values for high concentrations of PSA, an observation consistent with the phenomenon of the "hook effect." This effect was not observed when the sample was reanalyzed for PSA by a two-step procedure.